General information is requested concerning trimethoprim and sulfamethoxazole and liver damage. Is

Fråga: General information is requested concerning trimethoprim and sulfamethoxazole and liver damage. Is there any documentation of a dose independent relationship of this side-effect? If there is, what is the histology of the liver damage?

Sammanfattning: Hepatotoxicity is a known side-effect of trimethoprim-sulfamethoxazole. Several cases have been reported where idiosyncratic hepatitis occurred in susceptible patients after rechallenge with even small doses. Both primarily cholestatic and hepatocellular injuries have been demonstrated by liver biopsy or autopsy.

Svar: Trimethoprim-sulfamethoxazole (TMP-SMX) is known to cause liver damage (1-3) in the form of allergic or direct toxic effects (1,3). The hepatic reactions may be due mainly to the sulfonamide component which gives rise to 5.3 cases of the reaction per million defined daily doses (DDD) (4).

Several cases have been reported which seem to indicate that the hepatotoxicity caused by TMP-SMX appears to be an idiosyncratic reaction (5-7). A 70-year-old man exposed to TMP-SMX twice in a two month period developed rashes on both occasions. One month later he received only two tablets of the drug (160 mg trimethoprim and 800 mg sulfamethoxazole) and developed terminal hepatic failure followed by death. Autopsy revealed a severe hepatocellular injury with moderate cholestasis (5). Thies and Dull reported another case of hepatitis involving the inadvertent rechallenge with TMP-SMX in a patient with a previous episode of drug-induced hepatitis. Liver biopsy showed both cholestatic and cytotoxic changes (6). Cholestatic hepatitis with elevation of serum bilirubin has also been reported in a child whose liver biopsy showed mixed cellular infiltrate of the portal triads, absence of granulomas and eosinophilia (cf 1,7). 1 Drugline nr 03506 (year 1982) 2 Drugline nr 02998 (year 1982) 3 Drugline nr 02836 (year 1981) 4 Wiholm BE: Antibiotics Used in the Treatment of Urinary Tract Infections-Their Usage and Adverse Effects. Workshop: Treatment of Urinary Tract Infections, Läkemedelsverket 1990: (2) pp 75-89 5 Ransohof DF, Jacobs G: Terminal Hepatic Failure Following a Small Dose of Sulfamethoxazole-Trimethoprim. Gastroenterology 1981; 80: 816-819 6 Thies PW, Dull WL: Trimethoprim-sulfamethoxazole-induced cholestatic hepatitis Inadvertent rechallenge. Arch Intern Med 1984; 144: 1691-1692 7 Gutman LT: The use of trimethoprim-sulfamethoxazole in children: a review of adverse reactions and indications. Pediatr Infect Dis J 1984; 3: 349-357